Table 1.
Model Input Parameters for Analysis of Genotype Drug Resistance Testing at First-line Antiretroviral Therapy Failure in South Africa
| Variable | Estimate (Range Examined) | Data Sources |
|---|---|---|
| First-line ART failure cohort characteristics | ||
| Age, y, mean ± SD | 38.1 ± 4.6 | Initialization simulation |
| Male (%) | 55 | [13] |
| Distribution of initial CD4, cells/µL, mean ± SD | 173 ± 25 | [20, 21] |
| Median HIV RNA, log10 copies/mL | 4.9 | [18] |
| Prevalence of WT virus at first-line ART failure | 20% (1%–30%) | [21] |
| Natural history of disease | ||
| Mean monthly CD4 decline, cells/µL, by HIV RNA stratum | [40] | |
| >30 000 copies/mL | 6.4 | |
| 10 001–30 000 copies/mL | 5.4 | |
| 3001–10 000 copies/mL | 4.6 | |
| 501–3000 copies/mL | 3.7 | |
| 0–500 copies/mL | 3.0 | |
| Monthly risk of severe opportunistic diseasesa, range by CD4, % | [13] | |
| Active tuberculosis | 0.16–1.96 | |
| Other severe bacterial infection | 0.04–0.71 | |
| Other WHO stage III–IV event (mucocutaneous) | 0.03–2.26 | |
| Other WHO stage III–IV, nonspecific | 0.03–0.71 | |
| Non-WHO stage III–IV event | 0.25–1.67 | |
| Monthly risk of mild opportunistic diseasesa, range by CD4, % | [13] | |
| Fungal | 1.76–3.14 | |
| Other WHO stage II | 2.33–2.67 | |
| Monthly risk of HIV-related deatha, range by CD4, % | [13] | |
| No history of opportunistic infection | 0.11–4.0 | |
| History of opportunistic infection | 7.9–9.5 | |
| Antiretroviral therapy | ||
| Continued NNRTI-based ART after first-line ART failure (Geno WT cohort only) | ||
| Efficacyb | 45%c (10%–100%) | [20] |
| Second-line ART: PI-based (nucleoside-resistant virus) | ||
| Efficacyb | 80%c (10%–100%) | [22] |
| Second-line ART: PI-based (WT virus) | ||
| Efficacyb | 60% (10%–100%) | Assumption |
| Second-line ART: PI-based after failure of continued NNRTI-based ART (Geno WT cohort only) | ||
| Efficacyb | 60% (10%–100%) | Assumption |
| CD4 count increase at 24 wk (all strategies/cohorts) | 148 cells/µL | [23] |
| Probability of late failure, monthly, after 24 wk (all strategies/cohorts) | 1.3% (0%–30%) | [24–26] |
| Genotype-associated delays in ART switching, mo | 3 (0–12) | Assumption |
| Costs (2010 USD) | ||
| NNRTI-based ART, monthly | 10.33 | [2] |
| Lopinavir/ritonavir-based second-line ART, monthly | 51.07 (10–70) | [2] |
| Darunavir/etravirine/tenofovir-based third-line ART, monthlyd | 254.00 (25–300) | [2] |
| CD4 count test | 12.31 (6–23) | [41] |
| HIV RNA test | 61.55 (29–116) | [41] |
| Genotype test | 300 (50–600) | (Personal communication) |
| Discount rate | 3% (0%–5%) | [8] |
Abbreviations: ART, antiretroviral therapy; HIV, human immunodeficiency virus; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; SD, standard deviation; USD, US dollars; WHO, World Health Organization; WT, wild-type.
a Risk of opportunistic infection varies by CD4 stratum, classified as <50 cells/µL, 50–99 cells/µL, 100–199 cells/µL, 200–349 cells/µL, 350–499 cells/µL, or ≥500 cells/µL.
b Efficacy is modeled as the proportion with HIV RNA <400 copies/mL at week 24.
c In the base case, there is a 3-month genotype-associated delay in ART switching and a 5% absolute decrease in ART efficacy per 3-month delay (or 1.67% decrease per month) while remaining on a failing regimen. Therefore in the Geno WT cohort, the efficacy of continued NNRTI-based ART in the base case is 40% at 3 months, and in the Geno Resistant cohort, the efficacy of PI-based ART is 75% at 3 months.
d Third-line ART: modeled to be available only in sensitivity analyses.